IGF-1C hydrogel improves the therapeutic effects of MSCs on colitis in mice through PGE2-mediated M2 macrophage polarization
IGF-1C hydrogel improves the therapeutic effects of MSCs on colitis in mice through PGE2-mediated M2 macrophage polarization
复制标题
IGF-1C水凝胶通过PGE2介导的M2巨噬细胞极化提高MSC对小鼠结肠炎的治疗效果
DOI：
10.7150/thno.45434
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发表时间：
2020-01-01
期刊：
影响因子：
12.4
通讯作者：
Li, Zongji
中科院分区：
文献类型：
--
作者：
Cao, Xiaocang;Duan, Liyun;Li, Zongji
背景：间充质干细胞（MSC）为基础的治疗炎症性肠病（IBD）的治疗有很大的希望。为了优化和最大化MSC的治疗益处，我们研究了具有固定化IGF-1C结构域肽的壳聚糖（CS）基可注射水凝胶（CS-IGF-1C）和人胎盘来源的MSC（hP-MSC）的共移植是否可以改善小鼠结肠炎。方法：将IGF-1C固定于CS水凝胶上，制备IGF-1C水凝胶。用2，4，6-三硝基苯磺酸（TNBS）诱发小鼠结肠炎。我们首先应用hP-MSCs和CS-IGF-1C水凝胶原位注射治疗结肠炎，并利用分子成像技术对活性氧（ROS）进行实时成像，并通过生物发光成像（BLI）对移植的hP-MSCs进行追踪。同时观察CS-IGF-1C水凝胶对hP-MSCs分泌前列腺素E2（PGE 2）和M2巨噬细胞极化的影响。结果：CS-IGF-1C水凝胶可显著促进hP-MSC的增殖，并促进hP-MSC分泌PGE 2。此外，体内研究表明，CS-IGF-1C水凝胶促进hP-MSC存活，如通过BLI所观察到的，并显著减轻小鼠结肠炎，这可能是由极化的M2巨噬细胞产生的PGE 2和白细胞介素-10（IL-10）的hP-MSC产生介导的。结论：CS-IGF-1C水凝胶改善了移植的hP-MSCs的植入，改善了炎症反应，并通过PGE 2介导的M2巨噬细胞极化进一步促进了结肠炎的功能和结构恢复。水凝胶应用的分子成像方法和治疗策略为探索MSC在治疗IBD中的有前途的治疗潜力提供了一个通用的平台。
Background: Mesenchymal stem cell (MSC)-based therapies hold great promise for the treatment of inflammatory bowel disease (IBD). In order to optimize and maximize the therapeutic benefits of MSCs, we investigated whether cotransplantation of a chitosan (CS)-based injectable hydrogel with immobilized IGF-1 C domain peptide (CS-IGF-1C) and human placenta-derived MSCs (hP-MSCs) could ameliorate colitis in mice. Methods: IGF-1C hydrogel was generated by immobilizing IGF-1C to CS hydrogel. Colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice. We initially applied hP-MSCs and CS-IGF-1C hydrogel for the treatment of colitis by in situ injection, and molecular imaging methods were used for real-time imaging of reactive oxygen species (ROS) and tracking of transplanted hP-MSCs by bioluminescence imaging (BLI). Furthermore, the effects of CS-IGF-1C hydrogel on prostaglandin E2 (PGE2) secretion of hP-MSCs and polarization of M2 macrophages were investigated as well. Results: The CS-IGF-1C hydrogel significantly increased hP-MSC proliferation and promoted the production of PGE2 from hP-MSCs in vitro. Moreover, in vivo studies indicated that the CS-IGF-1C hydrogel promoted hP-MSC survival as visualized by BLI and markedly alleviated mouse colitis, which was possibly mediated by hP-MSC production of PGE2 and interleukin-10 (IL-10) production by polarized M2 macrophages. Conclusions: The CS-IGF-1C hydrogel improved the engraftment of transplanted hP-MSCs, ameliorated inflammatory responses, and further promoted the functional and structural recovery of colitis through PGE2-mediated M2 macrophage polarization. Molecular imaging approaches and therapeutic strategies for hydrogel application provide a versatile platform for exploring the promising therapeutic potential of MSCs in the treatment of IBD.